OBJECTIVE: To identify mutation of the PAX6 gene in a patient with congenital aniridia. METHODS: DNA was extracted from peripheral blood sample of the patient and analyzed by direct PCR-Sanger sequencing. RESULTS: The proband was found to harbor a heterozygous c.239T>A (p.Ile80Asn) mutation of the PAX6 gene. The same mutation was not found in his parents and 150 healthy controls. CONCLUSION A novel mutation of the PAX6 gene has been identified in a sporadic case with congenital aniridia.
Aniridia ; genetics ; Base Sequence ; Humans ; Mutation ; PAX6 Transcription Factor ; genetics ; Pedigree

BACKGROUNDMutations in PAX6 gene have been shown to be the genetic cause of aniridia, which is a severe panocular eye disease characterised by iris hypoplasia. However, there is no study to do genetic analysis of aniridia, although there are several case reports in China. Here, we describe a mutation analysis of PAX6 in a large Chinese family with aniridia.

METHODSGenomic DNA from venous blood samples was prepared. Haplotype analysis was performed with two genetic markers (D11S904 and D11S935). Fourteen exons of the PAX6 gene were amplified from genomic DNA. Polymerase chain reaction (PCR) products of each exon were analysed by single strand conformational polymorphism (SSCP). The PCR products having an abnormal pattern were sequenced to confirm the mutation.

RESULTSSignificant evidence for allele sharing in affected patients was detected suggesting that PAX6 mutation links to aniridia in this family. An extra band corresponding to exon 9 in PAX6 was found by single strand conformational polymorphism analysis in all the aniridia patients in this family, but not detected in the unaffected members. A mutation of C to T was detected by sequencing at the nucleotide 1080 that converts the Arg codon (CGA) to the termination codon (TGA).

CONCLUSIONSAniridia is caused by a nonsense mutation of PAX6 gene in the large Chinese kindred. Genetic test is important to prevent the transmission of aniridia to their offsprings in the kindred by prenatal diagnosis.

Aniridia ; genetics ; Eye Proteins ; genetics ; Female ; Homeodomain Proteins ; genetics ; Humans ; Male ; Mutation ; PAX6 Transcription Factor ; Paired Box Transcription Factors ; Pedigree ; Repressor Proteins ; genetics

OBJECTIVETo investigate the mutation of PAX6 gene in a Chinese family affected with congenital aniridia.

METHODSBlood samples were drawn from family members, and DNA was analyzed by direct sequencing.

RESULTSA heterozygous mutation (c.151 G>A) was identified in the PAX6 gene in the proband and other patients from the family. The same mutation was not found among unaffected family members and 160 unrelated healthy controls.

CONCLUSIONA novel mutation in the PAX6 gene has been identified in a Chinese family affected with aniridia.

Aniridia ; genetics ; Eye Proteins ; genetics ; Female ; Homeodomain Proteins ; genetics ; Humans ; Male ; Mutation ; PAX6 Transcription Factor ; Paired Box Transcription Factors ; genetics ; Repressor Proteins ; genetics

OBJECTIVETo identify potential mutation of the PAX6 gene in a family affected with congenital aniridia from northeastern China.

METHODSTwo patients were collected from the family and underwent full ophthalmologic examinations. Genomic DNA was extracted from all family numbers and 100 healthy controls. The coding regions and flanking sequence of the PAX6 gene were amplified by PCR amplification and subjected to bidirectional DNA sequencing.

RESULTSA nonsense mutation (c.718 C>T) was identified in exon 9 in both patients but not in other unaffected families or the 100 healthy controls. However, obvious difference was noted in the phenotype between the two patients. One of the patient has presented irregular cornea, which was infrequently reported.

CONCLUSIONA c.718C>T transitional mutation has been found to underlie the aniridia, which showed an autosomal dominant inheritance pattern in this northeastern Chinese family.

Aniridia ; genetics ; Eye Proteins ; genetics ; Female ; Homeodomain Proteins ; genetics ; Humans ; Male ; Mutation ; PAX6 Transcription Factor ; Paired Box Transcription Factors ; genetics ; Repressor Proteins ; genetics

OBJECTIVEThe PAX6 gene encodes a transcriptional regulator involved in oculogenesis and other developmental processes such as aniridia, a congenital condition characterized by the underdevelopment of the iris of eyes. The function of the PAX6 gene in these two conditions is still poorly defined. The purpose of this study is to identify the mutation of the PAX6 gene in a Chinese family with aniridia.

METHODSTwo aniridia patients collected from the family underwent full ophthalmologic examination. Genomic DNA was prepared from venous leukocytes of the two patients and five healthy individuals in the family, and 100 unrelated healthycontrols. Exons 4-13 and their immediate flanking sequences of the PAX6 gene was analyzed by PCR amplification, direct sequencing, and single-strand conformation polymorphism(SSCP).

RESULTSThe sequencing result revealed a novel PAX6 mutation in the two patients. It was a heterozygous mutation (IVS10+1G>A) at the boundary of exon 10 and intron 10. The mutation was also detected by SSCP analysis. It was not detected in the healthy relatives and unrelated controls.

CONCLUSIONAniridia is an autosomal dominant inheritable disease. A novel PAX6 gene mutation has been identified in the Northeastern Chinese family with aniridia. The genetic analysis suggested that this novel mutation in the PAX6 gene is capable of causing the classic aniridia phenotype.

Aniridia ; genetics ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Eye Abnormalities ; genetics ; Eye Proteins ; genetics ; Heterozygote ; Homeodomain Proteins ; genetics ; Humans ; Mutation ; PAX6 Transcription Factor ; Paired Box Transcription Factors ; genetics ; Pedigree ; Repressor Proteins ; genetics

OBJECTIVETo investigate the occurrence of supernumerary upper incisor teeth in Pax6-/- mouse fetuses and to provide a model to explore the role of Pax6 in the upper incisor development and the mechanism of supernumerary teeth involving Pax6.

METHODSTwenty Pax6-/- mouse fetuses of strain DEBA were isolated on E18.5 (embryonic day). The fetuses were sectioned serially in coronal plane and stained with haematoxylin and erosion, then the presence of supernumerary teeth in the upper anterior area was examined histologically, and also the number, morphology and structure of lower incisor germs and the first and second molar germs in the maxilla and mandible were observed histologically. Eighteen E18.5 mouse fetuses of strain DEBA with Pax6+/+ genotype were used as control.

RESULTSOf the 20 Pax6-/- fetuses examined, four possessed a single supernumerary tooth in the upper incisors' region. No supernumerary upper incisor teeth were observed in any of the 18 Pax6+/+ fetuses examined. In the regions of lower incisors and the first and second molars of the maxilla and mandible, no significant difference was observed between Pax6-/- and Pax6+/+ fetuses regarding the number, morphology and structure of tooth germs.

CONCLUSIONSThe results suggest that Pax6 played an important role in the development of upper incisor teeth in mice.

Animals ; Eye Proteins ; genetics ; Fetus ; Homeodomain Proteins ; genetics ; Incisor ; embryology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mutation ; PAX6 Transcription Factor ; Paired Box Transcription Factors ; genetics ; Repressor Proteins ; genetics ; Tooth Germ ; growth & development ; Tooth, Supernumerary ; genetics

OBJECTIVETo detect potential mutation in a Chinese family where two individuals were affected with hereditary congenital aniridia.

METHODSPeripheral blood samples were taken for genomic DNA extraction. All of the 15 exons of PAX6 gene were amplified with PCR. The product were purified with gel electrophoresis and sequenced.

RESULTSIn both patients, a novel deletion mutation (c.957-958delCA) in exon 13 of the PAX6 gene was identified, which has produced a terminator codon. The same mutation was not found in healthy controls.

CONCLUSIONA c.957-958delCA mutation of PAX6 gene is probably the cause of aniridia in this Chinese family.

Adult ; Aniridia ; genetics ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Child ; Exons ; Eye Proteins ; genetics ; Female ; Homeodomain Proteins ; genetics ; Humans ; Male ; Molecular Sequence Data ; PAX6 Transcription Factor ; Paired Box Transcription Factors ; genetics ; Pedigree ; Repressor Proteins ; genetics ; Sequence Deletion

BACKGROUNDPax-6 gene plays an important role in the process of eye development. This study was to determine the role of pax-6 in the axial myopia produced by hyperopic optical defocus and form deprivation in infant monkeys.

METHODSAmong seven normal infant rhesus monkeys (aged 1 to 1.5 months), five wore -3.00 D spectacle lenses over their right eyes and zero-powered lenses over their left eyes. Monocular form deprivation was produced by eyelid fusion in two monkeys. Ten weeks later, the monkeys were sacrificed by an overdose of barbiturates and their eyes were removed immediately. A 5 mm x 5 mm button of retina and sclera was taken from the posterior poles along with a 4-mm optic nerve. RNA was isolated separately from each of these three types of tissues. After that, reverse transcription polymerase chain reaction (RT-PCR) was used for determining gene expression in the retina, sclera and optic nerve. Semi-quantitative analyses were performed on the PCR products.

RESULTSAs expected, the optically induced hyperopic defocus and the form deprivation produced myopic growth. For the lens-treatment monkeys, pax-6 gene expression in the retinas of the defocused eyes was significantly higher than in the retinas of the left eyes (t = 5.703, P = 0.005). However, there were no analogous significant differences between pax-6 expression in the scleras or the optic nerves. For the two form-deprived monkeys, there were no obvious differences in pax-6 gene expression in the retinas or the optic nerves.

CONCLUSIONThe result that the expression of pax-6 was enhanced by hyperopic defocus in the infant monkey retina suggests that pax-6 may be involved in vision-dependent eye growth and emmetropization.

Animals ; Eye Proteins ; Gene Expression Regulation ; Homeodomain Proteins ; genetics ; Macaca mulatta ; Myopia ; metabolism ; Optic Nerve ; metabolism ; PAX6 Transcription Factor ; Paired Box Transcription Factors ; Repressor Proteins ; Retina ; metabolism ; pathology ; Reverse Transcriptase Polymerase Chain Reaction ; Sclera ; metabolism

OBJECTIVETo study the PAX6 gene mutation in a Chinese pedigree with congenital aniridia.

METHODSLinkage analysis was performed to the Chinese family with congenital aniridia using two microsatellite markers D11S904 and D11S935. Analysis of the PAX6 gene mutation was done by direct sequencing of the whole coding region and exon-intron boundaries of the PAX6 gene in all affected and unaffected individuals in the family.

RESULTSThe significant Lod Score of 3.01 was acquired at D11S935. Direct DNA sequence analysis identified a 1080C to T change in exon 9 of the patients, resulting in an Arginine substitution by a stop codon at codon 240 of the PAX6 gene, which was absent in the unaffected individuals in the family and 100 normal controls.

CONCLUSIONOur results indicate that mutation p.Arg240Ter of the PAX6 is the genetic basis of the Chinese family with congenital aniridia.

Adolescent ; Adult ; Aged ; Aniridia ; genetics ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Codon, Nonsense ; Eye Proteins ; genetics ; Female ; Homeodomain Proteins ; genetics ; Humans ; Male ; Microsatellite Repeats ; Molecular Sequence Data ; PAX6 Transcription Factor ; Paired Box Transcription Factors ; genetics ; Pedigree ; Repressor Proteins ; genetics

OBJECTIVETo identify the mutation in the PAX6 gene in a family with congenital aniridia and cataract.

METHODSTotal genomic DNA was extracted from peripheral blood leukocytes of 12 family members including three living affected members and 96 unrelated healthy controls. The coding exons 4-13 of the PAX6 gene with intronic flanking sequences were amplified by polymerase chain reaction (PCR). By comparing sequences of the affected members with that of normal individuals, the disease-causing mutation was detected by direct DNA sequencing.

RESULTSA PAX6 mutation was identified in the 3 patients, which did not exist in the unaffected members and unrelated healthy individuals. The nonsense mutation of C to T was detected at the nucleotide 1143, which converted the Arg codon (CGA) to a stop codon(TGA) (R261X) in exon 10.

CONCLUSIONThe mutation (R261X) detected in the present study is considered to result in the occurrence of congenital aniridia and cataract in the Chinese family.

Amino Acid Sequence ; Aniridia ; genetics ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Cataract ; congenital ; genetics ; Codon, Nonsense ; Eye Proteins ; genetics ; Homeodomain Proteins ; genetics ; Humans ; Male ; Molecular Sequence Data ; PAX6 Transcription Factor ; Paired Box Transcription Factors ; genetics ; Pedigree ; Repressor Proteins ; genetics